scholarly journals Molecular Docking Study of 3, 4- Dihydropyrimidone Derivatives as Novel Anti-inflammatory Agents

2021 ◽  
pp. 481-487
Author(s):  
Amit N. Panaskar ◽  
Ashish Jain ◽  
Pradeep Kumar Mohanty
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Docking Study ◽  
Protein Data Bank Code ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Enzyme Active Site ◽  
Cox 2 ◽  
Anti Inflammatory

Aim: Currently, researchers have developed a lot of new active substances as anti-inflammatory agents. One of the target proteins for anti-inflammatory agents is the selective COX-2 active site. Selective COX-2 inhibition is the regulator of the inflammatory reaction cascade. In this research, 3, 4- Dihydropyrimidone derivatives were used to design the anti-inflammatory agent through a selective COX-2 inhibition. The potential activity of 3, 4- Dihydropyrimidone derivatives maybe increase due to the preparation of the Schiff base with aromatic aldehydes. Selective COX-2 inhibition was required to predict their anti-inflammatory activity so, the aim in the present study, molecular docking study of 3,4- dihydropyrimidone derivatives have performed using COX-2 enzyme active site. Methodology: The molecular docking of 3, 4-dihydropyrimidone derivatives were carried out using AutoDock vina Ver.1.1.2. Twenty 3,4-dihydropyrimidone derivatives were docked into the COX-2 active site with Protein data bank code 3LN1. The interactions were evaluated based on the docking score. Celecoxib was used as the reference standard for this study. Results: Twenty 3, 4- dihydropyrimidone derivatives showed the approximate docking score -8.4 to -10.1 kcal/mol. Fourteen 3,4-dihydropyrimidone derivatives have a greater docking score compared to celecoxib used as a standard compound. Derivative D-1 had higher binding energy than other 3,4-dihydropyrimidone derivatives because it has the smallest docking score. Conclusion: All new 3,4-dihydropyrimidone derivatives are feasible to synthesize and performed their in-vitro evaluation.

Synthesis of new hexahydropyrimido[1,2-a]azepine derivatives bearing functionalized aryl and heterocyclic moieties as anti-inflammatory agents

2021 ◽  
Author(s):  
Hassanein H Hassanein ◽  
Doaa E Abdel Rahman ◽  
Marwa A Fouad ◽  
Rehab F Ahmed
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Study ◽  
In Vivo Studies ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

New hexahydropyrimido[1,2- a]azepine derivatives bearing functionalized aryl and heterocyclic moieties were synthesized as anti-inflammatory agents with better safety profiles. All synthesized compounds were assessed in vitro for their COX-1 and COX-2 inhibition activities. The most selective compounds, 2f, 5 and 6, were further evaluated for their in vivo anti-inflammatory activity and PGE2 inhibitory activity. To rationalize their selectivity, molecular docking within COX-1 and COX-2 binding sites was performed. Their physicochemical properties and drug-like nature profile were also calculated. The good activity and selectivity of compounds 2f, 5 and 6 were rationalized using a molecular docking study and supported by in vivo studies. These promising findings are encouraging for performing future investigations of these derivatives.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

scholarly journals Novel Group of AChE Reactivators—Synthesis, In Vitro Reactivation and Molecular Docking Study

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2291 ◽  
Author(s):  
David Malinak ◽  
Eugenie Nepovimova ◽  
Daniel Jun ◽  
Kamil Musilek ◽  
Kamil Kuca
Keyword(s):  
Molecular Docking ◽  
Molecular Modelling ◽  
Active Site ◽  
Molecular Design ◽  
Docking Study ◽  
The Novel ◽  
Molecular Docking Study ◽  
Causal Treatment ◽  
Modelling Study

The acetylcholinesterase (AChE) reactivators (e.g., obidoxime, asoxime) became an essential part of organophosphorus (OP) poisoning treatment, together with atropine and diazepam. They are referred to as a causal treatment of OP poisoning, because they are able to split the OP moiety from AChE active site and thus renew its function. In this approach, fifteen novel AChE reactivators were determined. Their molecular design originated from former K-oxime compounds K048 and K074 with remaining oxime part of the molecule and modified part with heteroarenium moiety. The novel compounds were prepared, evaluated in vitro on human AChE (HssAChE) inhibited by tabun, paraoxon, methylparaoxon or DFP and compared to commercial HssAChE reactivators (pralidoxime, methoxime, trimedoxime, obidoxime, asoxime) or previously prepared compounds (K048, K074, K075, K203). Some of presented oxime reactivators showed promising ability to reactivate HssAChE comparable or higher than the used standards. The molecular modelling study was performed with one compound that presented the ability to reactivate GA-inhibited HssAChE. The SAR features concerning the heteroarenium part of the reactivator’s molecule are described.

scholarly journals Identification of Potent Inhibitors of COVID-19 Main Protease Enzyme by Molecular Docking Study

2020 ◽  
Author(s):  
pooja singh ◽  
Angkita Sharma ◽  
Shoma Paul Nandi
Keyword(s):  
Molecular Docking ◽  
Antiviral Drug ◽  
Cyclopiazonic Acid ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Protease Enzyme ◽  
Main Protease

<p>Within the span of a few months, the severe acute respiratory syndrome coronavirus, COVID-19 (SARS-CoV-2), has proven to be a pandemic, affecting the world at an exponential rate. It is extremely pathogenic and causes communicable infection in humans. Viral infection causes difficulties in breathing, sore throat, cough, high fever, muscle pain, diarrhea, dyspnea, and may lead to death. Finding a proper drug and vaccines against this virus is the need of the hour. The RNA genome of COVID19 codes for the main protease M<sup>pro</sup>, which is required for viral multiplication. To identify possible antiviral drug(s), we performed molecular docking studies. Our screen identified ten biomolecules naturally present in <i>Aspergillus flavus</i> and <i>Aspergillus oryzae</i> fungi. These molecules include Aspirochlorine, Aflatoxin B1, Alpha-Cyclopiazonic acid, Sporogen, Asperfuran, Aspergillomarasmine A, Maltoryzine, Kojic acid, Aflatrem and Ethyl 3-nitropropionic acid, arranged in the descending order of their docking score. Aspirochlorine exhibited the docking score of – 7.18 Kcal/mole, higher than presently used drug Chloroquine (-6.2930522 Kcal/mol) and out of ten ligands studied four has docking score higher than chloroquine. These natural bioactive compounds could be tested for their ability to inhibit viral growth <i>in- vitro</i> and <i>in-vivo</i>.<b> </b></p>

scholarly journals Isoniazid-Isatin Hydrazone Derivatives: Synthesis, Antitubercular Activity and Molecular Docking Studies

2021 ◽  
Vol 18 (21) ◽  
pp. 39
Author(s):  
Mardi Santoso ◽  
Muhammad Riza Ghulam Fahmi ◽  
Yehezkiel Steven Kurniawan ◽  
Taslim Ersam ◽  
Sri Fatmawati ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Active Site ◽  
Antitubercular Activity ◽  
Docking Study ◽  
Positive Control ◽  
Tuberculosis H37rv ◽  
Molecular Docking Study

This study examined the synthesis of isoniazid-isatin hydrazone derivatives 5-7, followed by an investigation on the in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, and molecular docking. A yield of 81 - 92 % of these compounds was achieved, with structural characterization by spectroscopic methods (FTIR, NMR, HRMS). The in vitro antitubercular activity was evaluated against M. tuberculosis H37Rv, and the highest effect was observed in compound 7, with a minimum inhibitory concentration (MIC) of 0.017 mM, lower than rifampicin (MIC 0.048 mM), which served as the positive control. In addition, the molecular docking of 5-7 was performed to visualize the interaction of isoniazid-isatin hydrazone derivatives with the active site of InhA receptor, which was in agreement with the experimental data. The hydrogen bonding with Ser94 and pi-pi interaction with Phe41 and/or Phe97 on the InhA active site was pivotal for the antitubercular activity. HIGHLIGHTS Tuberculosis caused by Mycobacterium tuberculosis is one of the top ten leading causes of death globally The first and second lines of antituberculosis drugs are the prevalent treatment for this disease, but they show several drawbacks and are exacerbated by the occurrence of drug resistance The isoniazid-isatin hydrazone derivatives were designed through molecular hybridization and synthesized effectively and exhibited moderate to high activity against tuberculosis H37Rv Molecular docking study demonstrated that the hydrogen bonding with Ser94 and the pi-pi interaction with Phe41 and/or Phe97 are important for antitubercular activity GRAPHICAL ABSTRACT

scholarly journals Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 599 ◽  
Author(s):  
Mansour Sobeh ◽  
Samar Rezq ◽  
Mohammed Cheurfa ◽  
Mohamed A.O. Abdelfattah ◽  
Rasha M.H. Rashied ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Secondary Metabolites ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Thymus Algeriensis ◽  
Comprehensive Comparison ◽  
Cox 2 ◽  
Anti Inflammatory

This study aimed to investigate the chemical composition, and evaluate the antioxidant, anti-inflammatory, anti-pyretic, and the analgesic properties of methanol extracts from the leaves of Thymus algeriensis and Thymus fontanesii (Lamiaceae). Thirty-five secondary metabolites were characterized in both extracts using HPLC-PDA-ESI-MS/MS. Phenolic acids, mainly rosmarinic acid and its derivatives, dominated the T. algeriensis extract, while the phenolic diterpene carnosol and the methylated flavonoid salvigenin, prevailed in T. fontanesii extract. Molecular docking study was carried out to estimate the anti-inflammatory potential and the binding affinities of some individual secondary metabolites from both extracts to the main enzymes involved in the inflammation pathway. In vitro enzyme inhibitory assays and in vivo assays were used to investigate the antioxidant and anti-inflammatory activities of the extracts. Results revealed that both studied Thymus species exhibited antioxidant, anti-inflammatory, analgesic, and antipyretic effects. They showed to be a more potent antioxidant than ascorbic acid and more selective against cyclooxygenase (COX-2) than diclofenac and indomethacin. Relatively, the T. fontanesii extract was more potent as COX-2 inhibitor than T. algeriensis. In conclusion, Thymus algeriensis and Thymus fontanesii may be interesting candidates for the treatment of inflammation and oxidative stress-related disorders.

Identification of natural compounds with analgesic and anti-inflammatory properties using machine learning and molecular docking studies

2021 ◽  
Vol 18 ◽  
Author(s):  
Mohammad Firoz Khan ◽  
Ridwan Bin Rashid ◽  
Mohammad A. Rashid
Keyword(s):  
Machine Learning ◽  
Natural Products ◽  
Molecular Docking ◽  
High Throughput ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Natural Sources ◽  
Cox 2 ◽  
Anti Inflammatory

Background: Natural products have been a rich source of compounds for drug discovery. Usually, compounds obtained from natural sources have little or no side effects, thus searching for new lead compounds from traditionally used plant species is still a rational strategy. Introduction: Natural products serve as a useful repository of compounds for new drugs; however, their use has been decreasing, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. To address this unmet demand, we have developed and validated a high throughput in silico machine learning screening method to identify potential compounds from natural sources. Methods: In the current study, three machine learning approaches, including Support Vector Machine (SVM), Random Forest (RF) and Gradient Boosting Machine (GBM) have been applied to develop the classification model. The model was generated using the cyclooxygenase-2 (COX-2) inhibitors reported in the ChEMBL database. The developed model was validated by evaluating the accuracy, sensitivity, specificity, Matthews correlation coefficient and Cohen’s kappa statistic of the test set. The molecular docking study was conducted on AutoDock vina and the results were analyzed in PyMOL. Results: The accuracy of the model for SVM, RF and GBM was found to be 75.40 %, 74.97 % and 74.60 %, respectively which indicates the good performance of the developed model. Further, the model has demonstrated good sensitivity (61.25 % - 68.60 %) and excellent specificity (77.72 %- 81.41 %). Application of the model on the NuBBE database, a repository of natural compounds, led us to identify a natural compound, enhydrin possessing analgesic and anti-inflammatory activities. The ML methods and the molecular docking study suggest that enhydrin likely demonstrates its analgesic and anti-inflammatory actions by inhibiting COX-2. Conclusion: Our developed and validated in silico high throughput ML screening methods may assist in identifying drug-like compounds from natural sources.

SYNTHESIS AND INVESTIGATION OF ANTI-ACETYLCHOLINESTERASE ACTIVITY IN SILICO AND IN VITRO OF SOME CHALCONES

2012 ◽  
pp. 98-106
Author(s):  
Thai Son Tran ◽  
Khac Minh Thai ◽  
Thanh Dao Tran
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Condensation Reaction ◽  
Acetylcholinesterase Inhibitors ◽  
Acetylcholinesterase Activity ◽  
The Elderly ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ic50 Value

Background: Alzheimer is a major cause of dementia in the elderly and acetylcholinesterase inhibitors are used to treat the symptoms of this disease. Recently, chalcones have been reported as potential acetylcholinesterase inhibitors. Materials and methods: In this study, Claisen-Schmidt condensation reaction was applied to synthesize chalcones. Anti-acetylcholinesterase activity of these chalcones was determined by Ellman method. Molecular docking studies on acetylcholinesterase were performed to explain the interaction between these chalcone analogues and acetylcholinesterase active site at molecular level. Results: A total of twenty chalcones were synthesized and determined for in vitro anti-acetylcholinesterase activity. The results indicated that six compounds having IC50 value below 100 µM, three compounds having IC50 value in the range of 100 µM and 300 µM, the rest having IC50 value above 300 µM. Chalcone S17 (4’-amino-2-chlorochalcone) shows the strongest anti-acetylcholinesterase activity in the investigated group with IC50 value of 36.10 µM. In combination with the results of the in vitro anti-acetylcholinesterase activity, molecular docking study is used to explain the interaction between chalcone molecules and their active site, and the structure-activity relationship is abstracted. Conclusions: Our study indicated that the 2’-hydroxychalcones with halogen functional groups on B ring are strong acetylcholinesterase inhibitors. Chalcone S17 (4’-amino-2-chlorochalcone) could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors. Keywords: acetylcholinesterase, AChE, Alzheimer, chalcon, docking. Key words: A cetylcholinesterase, AChE, Alzheimer, chalcon, docking

Synthesis, in vitro COX-1/COX-2 inhibition testing and molecular docking study of novel 1,4-benzoxazine derivatives

2019 ◽  
Vol 43 (26) ◽  
pp. 10305-10317 ◽  
Author(s):  
Mohammedumar M. Shaikh ◽  
Anuj P. Patel ◽  
Shivani P. Patel ◽  
Kishor H. Chikhalia
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Cox 1

The present work deals with an efficient and straightforward synthesis, biological activity and molecular docking study of novel 1,4-benzoxazine derivatives.

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